A DNA aptamer prevents influenza infection by blocking the receptor binding region of the viral hemagglutinin

被引:129
作者
Jeon, SH [1 ]
Kayhan, B [1 ]
Ben-Yedidia, T [1 ]
Arnon, R [1 ]
机构
[1] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel
关键词
D O I
10.1074/jbc.M409059200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Influenza A virus infection is a major source of morbidity and mortality worldwide. Current means of control for influenza are based on prophylaxis by vaccines and on treatment by the available specific influenza neuraminidase inhibitor drugs. The approach taken in the present study is to prevent and/or ameliorate influenza infection by site-specific blocking of the viral binding to host cell receptors. We describe a novel oligonucleotide, known also as an aptamer, which has been designed to complement the receptor-binding region of the influenza hemagglutinin molecule. It was constructed by screening a DNA library and processing by the selective evolution of ligands by exponential enrichment (SELEX) procedure. We show that this DNA aptamer is indeed capable of inhibiting the hemagglutinin capacity of the virus, as well as in the prevention of viral infectivity in vitro, in tissue culture. Furthermore, it inhibits viral infection by different influenza strains in an animal model, as manifested by 90-99% reduction of virus burden in the lungs of treated mice. The mode of action of this aptamer is by blocking the binding of influenza virus to target cell receptors and consequently prevention of the virus invasion into the host cells.
引用
收藏
页码:48410 / 48419
页数:10
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